Identifying progressive gene network perturbation from single-cell RNA-seq data

Identifying the gene regulatory networks that control development or disease is one of the most important problems in biology. Here, we introduce a computational approach, called PIPER ( P rogressIve network PER turbation), to identify the perturbed genes that drive differences in the gene regulatory network across different points in a biological progression. PIPER employs algorithms tailor-made for single cell RNA sequencing (scRNA-seq) data to jointly identify gene networks for multiple progressive conditions. It then performs differential network analysis along the identified gene networks to identify master regulators. We demonstrate that PIPER outperforms state-of-the-art alternative methods on simulated data and is able to predict known key regulators of differentiation on real scRNA-Seq datasets.